Beata Szefler*, Przemysław Czeleń, Adam Szczepanik and Piotr Cysewski Pages 1775 - 1783 ( 9 )
Background: Cisplatin (CisPt) has a well-recognized anticancer activity by interacting with DNA and inducing programmed cell death. However, theoretical studies performed on the molecular level suggest that such nonspecific interactions can also take place with many competitive compounds, such as vitamins containing aromatic rings with lone-pair orbitals.
Objective: This work is a theoretical study on the initial Pt-N7(N1) bond formation with vitamins from B group and their comparison with values characterizing native purines.
Methods: Geometries of studied structures were optimized with an aid of Gaussian 09 using the B3LYP functional with the 6-31G** basis set. Atomic orbitals of platinum were represented by the lanl2dz basis. Solvation free energies were evaluated by a self-consistent reaction field (SCRF) approach. A dielectric constant of 78 for water was used in the PCM continuum model computations along with radii Bondii.
Results: The affinities of mono-aqua cis~[Pt(NH3)2Cl(H2O)]+ and di-aqua cis~ [Pt(NH3)2(H2O)2]2+ derivatives of Cisplatinum toward compounds belonging to the group of eight B vitamins were studied and compared to interactions with canonical purines. All the values of ΔGr unambiguously indicate that reactions with cisPt-diaqua are more preferable, but the comparison of ΔGr values obtained for compounds from vitamin B group and the ones characterizing complexes created by Guanine molecules indicates higher affinity of cisPt monomers toward purines.
Conclusion: Based on the observations, the regular intake of vitamin-rich beetroot or carrot juices is strongly discouraged during anticancer therapy using CisPt drug. To confirm the results of the performed computational study, detailed clinical trials should be performed.
Cisplatin (Cisplatinum, CisPt), platinum-based drugs, lung cancer, cancer treatment, vitaminum B, thiamine (B1), pyridoxal phosphate (B6), niacin (B3), riboflavin (B2).
Department of Physical Chemistry, Faculty of Pharmacy, Collegium Medicum, Nicolaus Copernicus University, Kurpinskiego 5, 85-096, Bydgoszcz, Department of Physical Chemistry, Faculty of Pharmacy, Collegium Medicum, Nicolaus Copernicus University, Kurpinskiego 5, 85-096, Bydgoszcz, The Kuyavian and Pomeranian Pulmonology Centre in Bydgoszcz Lung Cancer Treatment Department, Seminaryjna 1, 84-326, Bydgoszcz, Department of Physical Chemistry, Faculty of Pharmacy, Collegium Medicum, Nicolaus Copernicus University, Kurpinskiego 5, 85-096, Bydgoszcz